This application is a supplement to a recently funded randomized controlled trial, Phytoestrogens in Progression of Atherosclerosis. This supplement is focused on the effect of isoflavone-rich soy protein supplementation on cognition in postmenopausal women. Fear and discontent with traditional hormone therapy has resulted in an escalating use of soy products as a postmenopausal therapeutic alternative. Current information derived from clinical trials of the efficacy of soy on cognition is limited since studies have been of short duration (mostly weeks and months) and conducted in small sample sizes. Data concerning the effects of soy on cognition from long-term trials conducted in a large cohort of postmenopausal women are missing. As such, the design, duration and size of the parent trial make it an ideal platform upon which to adequately assess the effects of isoflavone-rich soy protein supplementation on cognition in postmenopausal women. Since the central portion of the clinical trial has been funded, a very robust database will be obtained at considerable savings. The objective of this supplement is to investigate the effect of isoflavone-rich soy protein supplementation on cognition in 300 healthy postmenopausal women in a randomized, double-blind, placebo controlled, 2.5 year trial. We hypothesize that intake of isoflavone-rich soy protein over a 2.5- year trial period that replicates the consumption by a typical Asian population, will have a positive effect on cognitive change. The Specific Aims are: 1) To test the hypothesis, in a randomized, double-blind, placebo-controlled, 2.5 year trial, that longitudinal changes in cognitive function will be improved with administration of isoflavone-rich soy protein supplementation in healthy postmenopausal women; and, 2) To evaluate the longitudinal associations between changes in blood levels of isoflavones and changes in cognitive function. Isoflavone-rich soy protein supplementation may provide a safe and effective means for extending premenopausal protection from cognitive decline afforded by endogenous estrogen into menopause without the increased risk of breast cancer, endometrial cancer, ovarian cancer, and thromboembolism associated with traditional hormone therapy, and without the side effects that limit long-term use and compliance for most women. [unreadable] [unreadable]